Osteoporosis is a progressive condition in which bones gradually lose their strength and density. An estimated 1 million older Americans suffer broken bones (typically wrist, spinal vertebrae and hips) because of osteoporosis. Women typically account for the vast majority of injuries caused by osteoporosis.
Normally, bone is continuously removed by osteoclasts and is replaced with new bone that is produced by osteoblasts. Bone loss results when the balance of the constructive and destructive processes is tipped from equilibrium toward a loss of calcium and other bone components. Osteoporosis is typically caused by either environmental or genetic factors. Environmental factors include aging and endocrine disease (i.e., hyperthyroidism, hypogonadism, Cushing's Syndrome). Genetic factors include abnormal estrogen receptor gene, osteogenesis imperfecta tarda, and homocysteinuria.
One typical treatment for osteoporosis is hormone replacement therapy, however, the efficacy of such treatment is in doubt (Hulley, S., et al. J. Am. Med. Assoc. 280:605–613 (1998)). Another treatment involves the use of bisphosphonates (e.g., alendronate, risedronate), raloxifene, and/or nasal calcitonin. All of the aforementioned antiresorptive agents currently approved for the treatment decrease bone resorption but do not induce new bone formation. Studies have shown that antiresorption agents may in fact prevent new bone formation and may contribute to increased fractures in patients who have been taking these agents from prolonged periods (Goodman R. L., New Engl. J. Med. 344(22):1720–1721 (2001); Mashiba, T., et al., Bone 28(5):424–31 (2001)). In addition, bisphosphonates can cause side effects involving the gastrointestinal tract.
Because osteoporosis is a common disease of aging and because the elderly population in the United States continues to grow, there is a clear need for new treatments for osteoporosis. Additionally, new treatments that could promote the formation of bone and that could prophylactically treat bone disorders are needed. Such new treatments should have minimal side effects, particularly systemic side effects.